Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies

Q1 Health Professions

Animal models and experimental medicine Pub Date : 2024-07-09 DOI:10.1002/ame2.12452

A. M. Abu Ahmed, Md. Atiar Rahman, Farjana Sharmen, A. S. M. Ali Reza, Md. Shahidul Islam, Md. Mamunur Rashid, Md. Khalid Juhani Rafi, Tanvir Ahmed Siddiqui, Md. Muzahid Ahmed Ezaj, Srabonti Saha, Md. Nazim Uddin, Walla Alelwani

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Abstract

Background

Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage–protecting effect of epiphytic Aerides odorata methanol extract (AODE).

Methods

The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand–receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses.

Results

AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), β-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (−11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity.

Conclusion

The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound–based animal study.

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超高效液相色谱-四极杆飞行时间质谱表征的 Aerides odorata Lour 提取物可减轻扑热息痛诱导的动物模型肝毒性，生化、分子和计算研究证明了这一点。

背景：许多种类的兰花都具有显著的保健作用，但对其生物功能的研究还不够充分。本研究探讨了附生兰甲醇提取物（AODE）对扑热息痛引起的肝损伤的保护作用：方法：通过分析AODE对肝功能参数、信使RNA（mRNA）表达和组织病理学结构的影响，研究AODE的保护作用。分子对接的配体与受体相互作用和网络药理学分析的多靶点相互作用证实了这些结果：结果表明：AODE 能明显降低组织的组织病理结构和组织表达：研究结果表明，通过进一步基于单一化合物的动物实验，AODE 可以成为药物性肝损伤的新型保肝靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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